Research Summary

Michelle's lab develops innovative approaches to discover chemical tools and drug leads to demonstrate 'druggability' of new target classes and to discover new targets for drug discovery. Areas of interest include protein-protein interactions, allosteric and scaffolding sites in enzymes, and orphan and neglected diseases. Michelle is Director of the Small Molecule Discovery Center, a collaborative research facility that includes high-throughput screening and medicinal chemistry ( The SMDC is a Cancer Center Core.

Research Funding

  • July 1, 2020 - June 30, 2024 - Discovery of Small Molecule Ligands for PHD1 Reader Domain of Histone Demethylase KDM5A , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA250459
  • September 5, 2018 - July 31, 2022 - Protein and small-molecule tools to probe the conformational dependence of the VCP/p97 protein-protein interaction network , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM130145
  • June 1, 2021 - May 31, 2022 - Bruker Sierra SPR-24 Pro , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10OD030265
  • March 23, 2016 - February 29, 2020 - A high content screen dissecting ciliogenesis and oncogenic Hedgehog signaling , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA181231


1990, Bryn Mawr College, Bryn Mawr, PA, B.A., Chemistry
1997, California Institute of Technology, Pasadena, CA, Ph.D., Chemistry
1999, Genentech, Inc, South San Francisco, CA and Sunesis Pharmaceuticals, Redwood City, CA, Postdoctoral fellowship, Protein Engineering

Honors & Awards

  • 1991
    European Traveling Fellowship, Bryn Mawr College
  • 1991-1992
    Blodgett Fellowship, General Electric Foundation
  • 1992-1995
    National Science Foundation Predoctoral Fellowship
  • 1995-1997
    National Institutes of Health Traineeship
  • 1997-1999
    Daymon Runyon-Walter Winchell Cancer Research Postdoctoral Fellowship
  • 2010
    Keynote address, Drug Discovery Chemistry, Protein-Protein Interactions (San Diego)
  • 2012
    Keynote speaker, EFMC-ISMC (Berlin)
  • 2013
    Keynote speaker, PPI-NET (London)
  • 2013
    Finalist, SLAS Innovation Award

Selected Publications

  1. Jiang Z, Kuo YH, Arkin MR. Autophagy Receptor-Inspired Antibody-Fusion Proteins for Targeted Intracellular Degradation. J Am Chem Soc. 2023 Sep 25.  View on PubMed
  2. Konstantinidou M, Visser EJ, Vandenboorn E, Chen S, Jaishankar P, Overmans M, Dutta S, Neitz RJ, Renslo AR, Ottmann C, Brunsveld L, Arkin MR. Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments. J Am Chem Soc. 2023 09 20; 145(37):20328-20343.  View on PubMed
  3. Visser EJ, Jaishankar P, Sijbesma E, Pennings MAM, Vandenboorn EMF, Guillory X, Neitz RJ, Morrow J, Dutta S, Renslo AR, Brunsveld L, Arkin MR, Ottmann C. From Tethered to Freestanding Stabilizers of 14-3-3 Protein-Protein Interactions through Fragment Linking. Angew Chem Int Ed Engl. 2023 Sep 11; 62(37):e202308004.  View on PubMed
  4. Emira J. Visser, Priyadarshini Jaishankar, Eline Sijbesma, Marloes A.M. Pennings, Edmee M.F. Vandenboorn, Xavier Guillory, R. Jeffrey Neitz, John Morrow, Shubhankar Dutta, Adam R. Renslo, Luc Brunsveld, Michelle R. Arkin, Christian Ottmann. From tethered to freestanding stabilizers of 14-3-3 protein-protein interactions via fragment linking. Angewandte Chemie. 2023 Aug 1.  View on PubMed
  5. Togo T, Tram L, Denton LG, ElHilali-Pollard X, Gu J, Jiang J, Liu C, Zhao Y, Zhao Y, Zheng Y, Zheng Y, Yang J, Fan P, Arkin MR, Härmä H, Sun D, Canan SS, Wheeler SE, Renslo AR. Systematic Study of Heteroarene Stacking Using a Congeneric Set of Molecular Glues for Procaspase-6. J Med Chem. 2023 07 27; 66(14):9784-9796.  View on PubMed
  6. Braxton JR, Altobelli CR, Tucker MR, Tse E, Thwin AC, Arkin MR, Southworth DR. The p97/VCP adapter UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions. bioRxiv. 2023 May 15.  View on PubMed
  7. Andlovic B, Heilmann G, Ninck S, Andrei SA, Centorrino F, Higuchi Y, Kato N, Brunsveld L, Arkin M, Menninger S, Choidas A, Wolf A, Klebl B, Kaschani F, Kaiser M, Eickhoff J, Ottmann C. IFNα primes cancer cells for Fusicoccin-induced cell death via 14-3-3 PPI stabilization. Cell Chem Biol. 2023 Jun 15; 30(6):573-590.e6.  View on PubMed
  8. Pariury H, Fandel J, Bachl S, Ang KK, Markossian S, Wilson CG, Braun BS, Popescu B, Wohlfeil M, Beckman K, Xirenayi S, Roy RP, Olshen AB, Smith C, Arkin MR, Loh ML, Diaz-Flores E. Venetoclax and dinaciclib elicit synergistic preclinical efficacy against hypodiploid acute lymphoblastic leukemia. Haematologica. 2023 05 01; 108(5):1272-1283.  View on PubMed
  9. Van Horn KS, Wang D, Medina-Cleghorn D, Lee PS, Bryant C, Altobelli C, Jaishankar P, Leung KK, Ng RA, Ambrose AJ, Tang Y, Arkin MR, Renslo AR. Engaging a Non-catalytic Cysteine Residue Drives Potent and Selective Inhibition of Caspase-6. J Am Chem Soc. 2023 05 10; 145(18):10015-10021.  View on PubMed
  10. Kenanova DN, Visser EJ, Virta JM, Sijbesma E, Centorrino F, Vickery HR, Zhong M, Neitz RJ, Brunsveld L, Ottmann C, Arkin MR. A Systematic Approach to the Discovery of Protein-Protein Interaction Stabilizers. ACS Cent Sci. 2023 May 24; 9(5):937-946.  View on PubMed
  11. Somsen BA, Schellekens RJC, Verhoef CJA, Arkin MR, Ottmann C, Cossar PJ, Brunsveld L. Reversible Dual-Covalent Molecular Locking of the 14-3-3/ERRγ Protein-Protein Interaction as a Molecular Glue Drug Discovery Approach. J Am Chem Soc. 2023 03 29; 145(12):6741-6752.  View on PubMed
  12. Koleske ML, McInnes G, Brown JEH, Thomas N, Hutchinson K, Chin MY, Koehl A, Arkin MR, Schlessinger A, Gallagher RC, Song YS, Altman RB, Giacomini KM. Functional genomics of OCTN2 variants informs protein-specific variant effect predictor for Carnitine Transporter Deficiency. Proc Natl Acad Sci U S A. 2022 Nov 16; 119(46):e2210247119.  View on PubMed
  13. Tang Y, Kay A, Jiang Z, Arkin MR. LC3B Binds to the Autophagy Protease ATG4b with High Affinity Using a Bipartite Interface. Biochemistry. 2022 Nov 01; 61(21):2295-2302.  View on PubMed
  14. Leanne C. Sayles, Henry Martell, Amanda Koehne, Kean-Hooi Ang, Chris Wilson, Michelle Arkin, E. Alejandro Sweet-Cordero. Abstract B004: ATR-CHK1-WEE1 pathway is a critical dependency in the context of DNA damage and replicative stress in osteosarcoma. Clinical Cancer Research. 2022 Sep 15; 28(18_Supplement):b004-b004.  View on PubMed
  15. Julian Braxton, Chad Altobelli, Michelle Arkin, Daniel Southworth. Cryo-EM structures reveal dramatic remodeling of the p97 hexamer by the multi-domain adapter UBXD1. Acta Crystallographica Section A: Foundations and advances. 2022 Jul 29; 78(a1):a202-a202.  View on PubMed
  16. Jiang Z, Kuo YH, Zhong M, Zhang J, Zhou XX, Xing L, Wells JA, Wang Y, Arkin MR. Adaptor-Specific Antibody Fragment Inhibitors for the Intracellular Modulation of p97 (VCP) Protein-Protein Interactions. J Am Chem Soc. 2022 07 27; 144(29):13218-13225.  View on PubMed
  17. Theofilas P, Piergies AMH, Oh I, Lee YB, Li SH, Pereira FL, Petersen C, Ehrenberg AJ, Eser RA, Ambrose AJ, Chin B, Yang T, Khan S, Ng R, Spina S, Seeley WW, Miller BL, Arkin MR, Grinberg LT. Caspase-6-cleaved tau is relevant in Alzheimer's disease and marginal in four-repeat tauopathies: Diagnostic and therapeutic implications. Neuropathol Appl Neurobiol. 2022 08; 48(5):e12819.  View on PubMed
  18. Chin MY, Ang KH, Davies J, Alquezar C, Garda VG, Rooney B, Leng K, Kampmann M, Arkin MR, Kao AW. Phenotypic Screening Using High-Content Imaging to Identify Lysosomal pH Modulators in a Neuronal Cell Model. ACS Chem Neurosci. 2022 05 18; 13(10):1505-1516.  View on PubMed
  19. Hulce KR, Jaishankar P, Lee GM, Bohn MF, Connelly EJ, Wucherer K, Ongpipattanakul C, Volk RF, Chuo SW, Arkin MR, Renslo AR, Craik CS. Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine. Cell Chem Biol. 2022 05 19; 29(5):785-798.e19.  View on PubMed
  20. Kim GJ, Mo H, Liu H, Okorie M, Chen S, Zheng J, Li H, Arkin M, Huang B, Guo S. In Vivo Dopamine Neuron Imaging-Based Small Molecule Screen Identifies Novel Neuroprotective Compounds and Targets. Front Pharmacol. 2022; 13:837756.  View on PubMed

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